The CAPRISA Clinical Trials Unit for AIDS/Tuberculosis Prevention and Treatment (CAPRISA CTU), strategically located in KwaZulu-Natal, South Africa, at the epicenter of one of the world's most severe HIV and tuberculosis (TB) epidemics, has recently made significant scientific contributions on tenofovir gel and pre-exposure prophylaxis, HIV-TB treatment, prevention of breastfeeding transmission, and immunity with broadly neutralizing antibodies. The scientific team includes investigators who have served at the highest levels in Network leadership. During the current funding cycle, 2,854 participants have been enrolled in 25 protocols to date, with retention rates usually exceeding 90% and data quality scores exceeding 95%. The CAPRISA CTU comprises 4 components; firstly, experienced leadership, senior investigators and CTU coordinator; secondly, an administrative and governance component; thirdly, 10 research support cores; and fourthly, 4 Clinical Research Sites (CRSs). The eThekwini CRS for vaccine, microbicide and adult HIV treatment studies, is located in central Durban adjoining a local clinic that annually treats 40,000 patients with sexually transmitted infections (HIV prevalence of 59.3% (CI: 56.5-62.0) and HIV incidence rate of 6.4 per 100 person-years (CI: 2.6-13.2)) as well as 3,500 new TB cases, two thirds of whom are co-infected with HIV. At the rural Vulindlela CRS for integrated prevention, vaccine and microbicide studies, the HIV prevalence among young women is 35.7% (CI: 32.7-38.8) and the HIV incidence rate is 6.5 per 100 person-years (CI: 4.4-9.2). In this community, HIV incidence is 10.2 per 100 person-years (CI: 4.1-20.9) in women under 20 years. The Springfield CRS for adult HIV/TB treatment studies is located at a regional referral hospital that treated 2,359 MDR-TB and 206 XDR-TB patients (71% co-infected with HIV) in 2010. The Umlazi CRS for maternal/pediatric HIV studies is at a 1,200 bed hospital that provides pre-natal services to about 12,000 women annually (HIV prevalence: 39% (CI: 36.7-41.5)). The vertical transmission rate is 2.4% (CI 1.1-4.5) at birth but increases to 6.6% (CI 5.3-8.2) at 6-8 weeks post-partum due to breastfeeding. The CAPRISA CTU headquarters is located at the Nelson R Mandela School of Medicine and houses the Administration as well as the laboratory, pharmacy, data management and IT, community engagement, evaluation and quality assurance, financial management, bioethics, communication, regulatory compliance, and training Cores. The CTU's organizational structures (Leadership Group, Executive Committee and Community Advisory Board) and communication tools (regular meetings, video conferences, monthly newsletters and website) enable effective communication, management and governance in the unit. Overall, the CAPRISA CTU has diverse well-characterized high-risk populations, well established clinical facilities, accredited laboratories, pharmacies, and data management systems, strong community linkages, and extensive experience in conducting clinical trials, together with a track record of scientific innovation available to support the 5 Networks in developing new approaches to HIV and TB prevention and treatment.